DIVERSE PROSTAGLANDIN RECEPTORS ACTIVATE DISTINCT SIGNAL TRANSDUCTION PATHWAYS IN RAT MYOMETRIUM

Attempts were made to identify prostaglandin (PG) receptors in rat myometrium, according to the differential rank order of potencies displayed by the natural PGs and their analogues, both at the level of second messenger generation and contraction. In estrogen-treated rat myometrium, PGs [iloprost = PGI2 > PGE2 >> 16,16-dimethyl (DM)-PGE2; sulprostone = misoprostol = 0] induced adenosine 3',5'-cyclic monophosphate generation, indicating the contribution of a PGI2 receptor. The generation of inositol phosphates was stimulated by PGs (PGF2-alpha > PGD2 >> PGE2 = DM-PGE2 >> iloprost > sulprostone = misoprostol = 0), reflecting a PGF2-alpha-receptor-mediated process, which was insensitive to pertussis toxin (PTX). Contractions caused by PGF2-alpha were closely correlated to PGF2-alpha-receptor activation associated with the phospholipase C pathway. By contrast, contractions evoked by PGE2, equally mimicked by sulprostone and misoprostol, were abolished by PTX and were independent of phospholipase C activation. In the pregnant myometrium (day 21), the latter PGE-receptor-mediated mechanism also contributed to contractions caused by PGE2 (<mu-M concn). Phospholipase C activation was coupled not only to PGF2-alpha but also to PGE receptors and could be correlated with contractions induced by PGF2-alpha and PGE2 >mu-M concn). All PGs tested were coupled to inhibitory G protein-mediated adenylate cyclase inhibition, displaying an equipotency that did not allow characterization of the inhibitory PG receptors.